WNK463
WNK kinase inhibitor / Potent and selective pan-With-No-Lysine (WNK) kinase inhibitor (IC50’s: WNK1 = 5 nM, WNK2 = 1 nM, WNK3 = 6 nM, WNK4 = 9 nM), an important enzyme in blood pressure regulation and body fluid and electrolyte homeostasis.1 WNK kinases respond to hypertonicity by regulating SLC12 cation chloride transporters to rescue cell volume.2 WNK463 reduced migration of invasive types of breast cancer and attenuated tumor growth and metastatic burden in a mouse model.3 It induced a significant increase in NLRP3 inflammasome activation and pyroptosis specifically via WNK1 inhibition as well as increasing TNF production without inflammasome activation.4
Biochemicals & reagents
2012607-27-9
1) Yamada et al. (2016), Small-molecule WNK inhibition regulates cardiovascular and renal function; Nat. Chem. Biol. 12 896 2) Boyd-Shiwarski et al. (2022), WNK kinases sense molecular crowding and rescue cell volume via phase separation; Cell 185 4488 3) Jaykumar et al. (2021), WNK1 Enhances Migration and Invasion in Breast Cancer Models; Mol. Cancer Ther. 20 1800 4) Mayes-Hopfinger et al. (2021), Chloride sensing by WNK1 regulates NLRP3 inflammasome activation and pyroptosis; Nat. Commun. 12 4546
-20°C
TARGET: Kinase; Inflammasome -- PATHWAY: Pyroptosis; TNF -- RESEARCH AREA: Cell death -- DISEASE AREA: Hypertension; CancerInflammation